Angiotensin II is an active center of the renin-angiotensin system, and has powerful vasopressor action and stimulating action for the synthesis and secretion of aldosterone in the adrenal cortex. It is also known to be a substance causing hypertension. Its action is considered to be caused through a specific receptor on various target organs such as adrenal cortex, kidneys, arterioles and the peripheries of sympathetic nerves.
Known conventional examples of substances which show an antihypertensive effect by pharmacological inhibition of the renin-angiotensin system include angiotensin-converting enzyme inhibitors such as captopril and enarapril, angiotensin II antagonists and renin inhibitors. As angiotensin II antagonist out of these, saralasin ([Sar.sup.1, Ala.sup.8 ] AGII), an angiotensin II type peptide, and nonpeptide derivatives such as imidazole derivatives (Japanese Patent Laid-Open Nos. 7103/1981 and 71074/1981, and Japanese Language Laid-Open Publication (PCT) No. 501020/1991), pyrazole derivatives (Japanese Patent Laid-Open No. 218371/1991) and aminoazole derivatives (W093/17681) are already known.
The peptide derivatives, however, have difficulty in clinical applications because of their short in vivo half-life, lack of effectiveness upon oral administration and significant agonistic activities. Among the nonpeptide derivatives, none has been used clinically yet as drugs either.
With a view toward providing a clinically excellent drug under such circumstances, the present inventors have carried out an extensive investigation. As a result, it has been found that novel biphenylmethane derivatives represented by the following formula (I) have an excellent angiotensin II antagonist activity and are useful as therapeutics for circulatory diseases such as hypertension, heart diseases and cerebral apoplexy, leading to the completion of the invention.